The long term behavioral and biochemical alterations of offspring from cocaine treated gravid animals are unknown. Amphetamines are known to increase the activity of offspring throughout their lifetime. The goal of this proposal is to delineate cocaine-induced changes in offspring by treating gravid rats with cocaine or related drugs during all of gestation and examining the offspring for behavioral or biochemical changes. We hope to attain these specific aims: 1. determine the effects of maternal cocaine on early postnatal development and behavioral activity of the offspring and their behavioral responses to a dopamine antagonist during the first 6 months of life. 2. determine the effects of maternal cocaine on monoamine metabolite concentrations in various brain areas and the metabolic response of the dopaminergic system to a challenge by an antipsychotic drug. 3. determine the effects of maternal cocaine on brain monoamine receptor sensitivity with emphasis on striatal and mesolimbic dopamine receptors. 4. determine the effects of prenatal exposure to cocaine on learning and minimum reaction time, which relates to basal ganglia function. 5. determine whether administration of cocaine to gravid rats will alter levels of intraspecies aggression in the adult offspring. Gravid rats will receive injections of either saline, cocaine (15 mg/kg b.i.d.), amfonelic acid (AFA, 1.5 mg/kg) or amitryptiline (10 mg/kg) daily beginning 2 days after conception. The offspring will be sampled at 30, 60 and 180 days postnatal in order to determine age related changes in the measured parameters. Amitryptiline will be used to simulate the norepinephrine and 5- hydroxytryptamine re-uptake blockade of cocaine as well as the anticholinergic and local anesthetic effects and amfonelic acid will be used to simulate the dopamine re-uptake blockade and behavioral stimulation that are produced by cocaine. Thus, the components of cocaine's effects on the fetus will be separated. Examination of the results for cross correlations may allow determining the biochemical changes that are causing the behavioral alterations, which may allow targeting treatment for children of cocaine addicted mothers who may develop behavioral or learning problems.
